Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types

Hotspot mutations in splicing factor genes have been recently reported at high frequency in hematological malignancies, suggesting the importance of RNA splicing in cancer. We analyzed whole-exome sequencing data across 33 tumor types in The Cancer Genome Atlas (TCGA), and we identified 119 splicing factor genes with significant non-silent mutation patterns, including mutation over-representation, recurrent loss of function (tumor suppressor-like), or hotspot mutation profile (oncogene-like). Furthermore, RNA sequencing analysis revealed altered splicing events associated with selected splicing factor mutations. In addition, we were able to identify common gene pathway profiles associated with the presence of these mutations. Our analysis suggests that somatic alteration of genes involved in the RNA-splicing process is common in cancer and may represent an underappreciated hallmark of tumorigenesis

The complete mitochondrial genome of Amblyomma geoemydae (Ixodida: Ixodidae)

The complete mitochondrial genome of Amblyomma geoemydae is reported for the first time in this study. Its entire mitogenome is 14,780 bp in length, contained 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and two non-coding regions. The phylogenetic analysis by Maximum-likelihood method show that A. geoemydae and the others of genus Amblyomma are in the same clade, indicating that A. geoemydae belongs to the genus Amblyomma

Molecular Detection of Novel Borrelia Species, Candidatus Borrelia javanense, in Amblyomma javanense Ticks from Pangolins

A novel Borrelia species, Candidatus Borrelia javanense, was found in ectoparasite ticks, Amblyomma javanense, from Manis javanica pangolins seized in anti-smuggling operations in southern China. Overall, 12 tick samples in 227 (overall prevalence 5.3%) were positive for Candidatus B. javanense, 9 (5.1%) in 176 males, and 3 (5.9%) in 51 females. The phylogenetic analysis, based on the 16S rRNA gene and the flagellin gene sequences of the Borrelia sp., exhibited strong evidence that Candidatus B. javanense did not belong to the Lyme disease Borrelia group and the relapsing fever Borrelia group but another lineage of Borrelia. The discovery of the novel Borrelia species suggests that A. javanense may be the transmit vector, and the M. javanica pangolins should be considered a possible origin reservoir in the natural circulation of these new pathogens. To our knowledge, this is the first identification of a novel Borrelia species agent in A. javanense from pangolins. Whether the novel agent is pathogenic to humans is unknown and needs further research

Isolation and characterization of a pangolin-borne HKU4-related coronavirus that potentially infects human-DPP4-transgenic mice

Abstract We recently detected a HKU4-related coronavirus in subgenus Merbecovirus (named pangolin-CoV-HKU4-P251T) from a Malayan pangolin1. Here we report isolation and characterization of pangolin-CoV-HKU4-P251T, the genome sequence of which is closest to that of a coronavirus from the greater bamboo bat (Tylonycteris robustula) in Yunnan Province, China, with a 94.3% nucleotide identity. Pangolin-CoV-HKU4-P251T is able to infect human cell lines, and replicates more efficiently in cells that express human-dipeptidyl-peptidase-4 (hDPP4)-expressing and pangolin-DPP4-expressing cells than in bat-DPP4-expressing cells. After intranasal inoculation with pangolin-CoV-HKU4-P251, hDPP4-transgenic female mice are likely infected, showing persistent viral RNA copy numbers in the lungs. Progressive interstitial pneumonia developed in the infected mice, characterized by the accumulation of macrophages, and increase of antiviral cytokines, proinflammatory cytokines, and chemokines in lung tissues. These findings suggest that the pangolin-borne HKU4-related coronavirus has a potential for emerging as a human pathogen by using hDPP4

Experimental and Theoretical Study on the Structure, Optical Properties, and Growth of Metallic Silver Nanostructures in Ag3PO4

Theoretical and experimental studies were performed on the structure, optical properties, and growth of silver nanostructures in silver phosphate (Ag3PO4). This material was synthesized by the coprecipitation method and processed in a microwave-assisted hydrothermal system at 150 °C for different times. The structural behavior was analyzed by means of X-ray diffraction, Rietveld refinement, and Raman spectroscopy. Field emission gun scanning electron microscopy as well as transmission electron microscopy revealed the presence of irregular spherical-like Ag3PO4 microparticles; metallic silver nanostructures were found on their surfaces. The growth processes of Ag nanostructures when irradiated with an electron beam were explained by theoretical calculations. First-principles calculations, within a quantum theory of atoms in molecules framework, have been carried out to provide deeper insight and understanding of the observed nucleation and early evolution of Ag nanoparticles on Ag3PO4 crystals, driven by an accelerated electron beam from an electronic microscope under high vacuum. The Ag nucleation and formation is a result of structural and electronic changes of the AgO4 tetrahedral cluster as a constituent building block of Ag3PO4, consistent with Ag metallic formation. The optical properties were investigated by ultraviolet–visible spectroscopy and photoluminescence (PL) measurements at room temperature. PL properties of this phosphate were explained by the recombination phenomenon of electron–hole pairs via cluster-to-cluster charge transfer.The authors are grateful to Prometeo/2009/053 (Generalitat Valenciana), Ministerio de Economia y Competitividad (Spain), CTQ2012-36253-C03-02, Spanish Brazilian program (PHB2009-0065-PC), CAPES (203038 009607/2013-56), INCTMN (2008/57872-1), FAPESP (2012/14004-5; 2013/ 07296-2), CNPq (147001/2013-7; 573636/2008-7) for fi nancially supporting this research. We also acknowledge the Servei Informa tica, Universitat Jaume I, for the generous allotment of computer time